The present invention relates to the use of hydroxyphenyl-1,3-propanediones in the anti-microbial treatment of surfaces.
The hydroxyphenyl-1,3-propanediones used according to the invention correspond to formula: 
R1 and R2 are each independently of the other hydrogen, C1-C12alkyl, C1-C12alkoxy, trifluoro-C1-C3alkyl, phenyl or halogen;
R3 is a 5- or 6-membered heteroaromatic radical; thiophenyl; or a radical of formula: 
R4, R5, R6 and R7 are each independently of the other hydrogen, halogen, C1-C12alkyl, C1-C12alkoxy, carboxy or trifluoro-C1-C3alkyl.
C1-C12Alkyl and C1-C12alkoxy are straight-chain or branched alkyl and alkoxy radicals, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, amyl, isoamyl or tert-amyl, heptyl, octyl, isooctyl, nonyl, decyl, undecyl and dodecyl, and methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, amyloxy, isoamyloxy or tert-amyloxy, heptyloxy, octyloxy, isooctyloxy, nonyloxy, decyloxy, undecyloxy and dodecyloxy.
Preferred 6-membered heteroaromatic radicals are pyrazinyl, pyrimidinyl and pyridazinyl and especially pyridyl.
Examples of 5-membered heteroaromatic radicals are thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isoxazolyl and furazanyl.
The 5- or 6-membered heteroaromatic radicals may be unsubstituted or substituted by halogen, such as chlorine or bromine, by nitro, by C1-C5alkyl or by C1-C5alkoxy.
There are preferably used also compounds of formula: 
wherein
R1, R2, R3, R4, R5, R6 and R7 are as defined for formula (1).
Examples of compounds that can be used according to the invention correspond to formulae: 
The preparation of the compounds of formula (1) is carried out in a manner known per se in analogy to K. A. Thakar, D. D. Goswami , G. G. Pachpor , J.Ind.Chem.Soc. (I) (1973), 420-423 in a two-step reaction in accordance with the following scheme:
1st Step 
2nd Step 
The invention relates also to the process for the preparation of the compounds according to formula (1).
The process is carried out in a suitable solvent, usually at a temperature of from 0 to 50xc2x0 C. (1st step).
Preferably, pyridine is used as solvent at a temperature of 25xc2x0 C.
In a 2nd step the ester of formula (10) is rearranged to form the corresponding target compound of formula (1) by reaction with KOH powder in a suitable solvent, preferably pyridine, at a temperature of from 40 to 80xc2x0 C., preferably 50xc2x0 C.
A further process for the preparation of the compounds of formula (1) is solid phase synthesis on polymeric supports. 
For that purpose, R1- and R2-substituted hydroxyacetophenones of formula (9) are immobilised on a polystyrene-trityl chloride resin using suitable solvents, bases and catalysts, preferably dimethylformamide, N,N-diisopropylethylamine and 4-(N,N-dimethylamino)pyridine.
R3-Substituted esters are then heated with the polystyrene resin using suitable bases and solvents at temperatures of from 40 to 100xc2x0 C.
Preferably, sodium tert-butanolate and N,N-dimethylacetamide are used at a temperature of 80xc2x0 C.
For the removal of the compounds according to formula (1), the resins are treated with 5% trifluoroacetic acid in dichloromethane.
Some of the hydroxyphenyl-1,3-propanediones used according to the invention are known compounds, while some are new compounds.
The new compounds correspond to formula: 
The hydroxyphenyl-1,3-propanediones used according to the invention exhibit a pronounced antimicrobial action, especially against pathogenic gram-positive and gram-negative bacteria and also against bacteria of skin flora, e.g. Corynebacterium xerosis (bacteria that cause body odour), and also against yeasts and moulds. They are therefore especially suitable in the disinfection, deodorisation and general antimicrobial treatment of the skin and mucosa and of integumentary appendages (hair), more especially in the disinfection of the hands and of wounds.
They are therefore suitable as antimicrobial active ingredients in personal care preparations, for example shampoos, bath additives, hair-care products, liquid and solid soaps (based on synthetic surfactants and salts of saturated and/or unsaturated fatty acids), lotions and creams, deodorants, other aqueous or alcoholic solutions, e.g. cleansing solutions for the skin, moist cleansing cloths, oils or powders.
The invention therefore relates also to a personal care preparation comprising at least one compound of formula (1) as well as cosmetically tolerable carriers or adjuvants.
The personal care preparation according to the invention comprises from 0.01 to 15% by weight, preferably from 0.5 to 10% by weight, based on the total weight of the composition, of the hydroxyphenyl-1,3-propanedione compound of formula (1) and cosmetically tolerable adjuvants.
Depending upon the form of the personal care preparation, it will comprise, in addition to the hydroxyphenyl-1,3-propanedione compound of formula (1), further constituents, for example sequestering agents, colourings, perfume oils, thickening or solidifying (consistency regulator) agents, emolients, UV absorbers, skin-protective agents, antioxidants, additives that improve mechanical properties, such as dicarboxylic acids and/or Al, Zn, Ca and Mg salts of C14-C22fatty acids, and optionally additional preservatives and antimicrobial active ingredients.
The personal care preparation according to the invention may be formulated as a water-in-oil or oil-in-water emulsion, as an alcoholic or alcohol-containing formulation, as a vesicular dispersion of an ionic or non-ionic amphiphilic lipid, as a gel, a solid stick or as an aerosol formulation.
A water-in-oil or oil-in-water emulsion containing the hydroxyphenyl-1,3-propanedione compound of formula (1) comprises as cosmetically tolerable adjuvants preferably from 5 to 50% of an oily phase, from 5 to 20% of an emulsifier and from 30 to 90% water.
The oily phase may contain any oil suitable for cosmetic formulations, e.g. one or more hydrocarbon oils, a wax, a natural oil, a silicone oil, a fatty acid ester or a fatty alcohol. Preferred mono- or poly-ols are ethanol, isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol.
Compounds according to the invention may be contained in a variety of cosmetic preparations. Especially the following preparations, for example, come into consideration:
skin-care preparations, e.g. skin-washing and cleansing preparations in the form of tablet-form or liquid soaps, soapless detergents or washing pastes;
bath preparations, e.g. liquid (foam baths, milks, shower preparations) or solid bath preparations, e.g. bath cubes and bath salts;
skin-care preparations, e.g. skin emulsions, multi-emulsions or skin oils;
cosmetic personal care preparations, e.g. facial make-up in the form of day creams or powder creams, face powder (loose or pressed), rouge or cream make-up, eye-care preparations, e.g. eyeshadow preparations, mascara, eyeliner, eye creams or eye-fix creams, lip-care preparations, e.g. lipsticks, lip gloss, lip contour pencils, nail-care preparations, such as nail varnish, nail varnish removers, nail hardeners or nail hardener removers;
intimate hygiene preparations, e.g. intimate washing lotions or intimate sprays;
foot-care preparations, e.g. foot baths, foot powders, foot creams or foot balsams, special deodorants and antiperspirants or callous-removing preparations;
light-protective preparations, such as sun milks, lotions, creams and oils, sun blocks or tropicals, pre-tanning preparations or after-sun preparations;
skin-tanning preparations, e.g. self-tanning creams;
depigmenting preparations, e.g. preparations for bleaching the skin or skin-lightening preparations;
insect-repellents, e.g. insect-repellent oils, lotions, sprays or sticks;
deodorants, such as deodorant sprays, pump-action sprays, deodorant gels, sticks or roll-ons;
antiperspirants, e.g. antiperspirant sticks, creams or roll-ons;
preparations for cleansing and caring for blemished skin, e.g. soapless detergents (solid or liquid), peeling or scrub preparations or peeling masks;
hair-removal preparations in chemical form (depilation), e.g. hair-removing powders, liquid hair-removing preparations, cream- or paste-form hair-removing preparations, hair-removing preparations in gel form or aerosol foams;
shaving preparations, e.g. shaving soap, foaming shaving creams, non-foaming shaving creams, foams and gels, preshave preparations for dry shaving, aftershaves or after-shave lotions;
fragrance preparations, e.g. fragrances (eau de Cologne, eau de toilette, eau de parfum, parfum de toilette, perfume), perfume oils or cream perfumes;
dental-care, denture-care and mouth-care preparations, e.g. toothpastes, gel tooth-pastes, tooth powders, mouthwash concentrates, anti-plaque mouthwashes, denture cleaners or denture fixatives;
cosmetic hair-treatment preparations, e.g. hair-washing preparations in the form of shampoos and conditioners, hair-care preparations, e.g. pretreatment preparations, hair tonics, styling creams, styling gels, pomades, hair rinses, treatment packs, intensive hair treatments, hair-structuring preparations, e.g. hair-waving preparations for permanent waves (hot wave, mild wave, cold wave), hair-straightening preparations, liquid hair-setting preparations, foams, hairsprays, bleaching preparations, e.g. hydrogen peroxide solutions, lightening shampoos, bleaching creams, bleaching powders, bleaching pastes or oils, temporary, semi-permanent or permanent hair colourants, preparations containing self-oxidising dyes, or natural hair colourants, such as henna or camomile.
An antimicrobial soap has, for example, the following composition:
0.01 to 5% by weight of the compound of formula (1)
0.3 to 1% by weight titanium dioxide
1 to 10% by weight stearic acid
ad 100% soap base, e.g. the sodium salts of tallow fatty acid and coconut fatty acid or glycerol.
A shampoo has, for example, the following composition:
0.01 to 5% by weight of the compound of formula (1)
12.0% by weight sodium laureth-2-sulfate
4.0% by weight cocamidopropyl betaine
3.0% by weight NaCl and
water ad 100%.
A deodorant has, for example, the following composition:
0.01 to 5% by weight of the compound of formula (1)
60% by weight ethanol
0.3% by weight perfume oil and
water ad 100%.
Example of an O/W emulsion:
0.01-5% by weight of the compound of formula (1)
12% by weight glyceryl stearate
6% by weight paraffin oil
6% by weight caprylic/capric triglyceride
4% by weight glycerol
0.2% by weight disodium EDTA
1.0% by weight citric acid (20%) and
65.8-70.8% by weight water.
Example of an O/W emulsion:
0.01-5% by weight of the compound of formula (1)
3.5% by weight PEG-30 dipolyhydroxystearate
10.0% by weight paraffin oil
4% by weight caprylic/capric triglyceride
4% by weight dicaprylic ether
0.2% by weight disodium EDTA
3.4% by weight glycerol and
69.9-74.9% by weight water.
The invention relates also to an oral care composition, comprising
0.01 to 15% by weight, based on the total weight of the composition, of the compound of formula (1) and orally tolerable adjuvants.
Example of an oral care composition:
10% by weight sorbitol
10% by weight glycerol
15% by weight ethanol
15% by weight propylene glycol
0.5% by weight sodium lauryl sulfate
0.25% by weight sodium methylcocyl taurate
0.25% by weight polyoxypropylene polyoxyethylene block copolymer
0.10% by weight peppermint flavouring
0.1 to 0.5% by weight of a compound of formula (1) and
48.6% by weight water.
The oral care composition according to the invention may be, for example, in the form of a gel, a paste, a cream or an aqueous preparation (mouthwash).
The oral care composition according to the invention may also comprise compounds that release fluoride ions which are effective against the formation of caries, for example inorganic fluoride salts, e.g. sodium, potassium, ammonium or calcium fluoride, or organic fluoride salts, e.g. amine fluorides, which are known under the trade name Olafluor.
The hydroxyphenyl-1,3-propanediones of formula (1) used according to the invention are also suitable for the antimicrobial treatment of textile fibre materials. Such materials are undyed and dyed or printed fibre materials, e.g. of silk, wool, polyamide, polyester, poly-propylene or polyurethanes, and especially cellulose-containing fibre materials of all kinds. Such fibre materials are, for example, natural cellulose fibres, such as cotton, linen, jute and hemp, as well as cellulose and regenerated cellulose. Preferred suitable textile fibre materials are made of cotton.
The compounds of formula (1) are also suitable, alone or in combination with other antimicrobial substances, for preserving cosmetic products, e.g. shampoos, bath additives, hair-care preparations, liquid and solid soaps (based on synthetic surfactants and salts of saturated and/or unsaturated fatty acids), lotions and creams, deodorants, other aqueous or alcoholic solutions, e.g. cleansing solutions for the skin, moist cleansing cloths, oils or powders and household products, for example in washing and cleaning formulations, e.g. in liquid or powder washing agents or softeners.
The hydroxyphenyl-1,3-propanediones used according to the invention are also suitable for imparting antimicrobial properties to plastics, e.g. polyethylene, polypropylene, polyurethane, polyester, polyamide, polycarbonate, latex etc. Fields of use therefor are, for example, floor coverings, plastics coatings, plastics container and packaging materials, kitchen and bathroom utensils (e.g. brushes, shower curtains, sponges, bathmats), latex filter materials (air and water filters), plastics articles used in the field of medicine, e.g. dressing materials, syringes, catheters etc., so-called xe2x80x9cmedical devicesxe2x80x9d, gloves and mattresses.
Paper, for example papers used for hygiene purposes, may also be provided with antimicrobial properties using the hydroxyphenyl-1,3-propanediones according to the invention.
It is also possible for nonwovens, e.g. nappies/diapers, sanitary towels, panty liners, and cloths for hygiene and household uses, to be provided with antimicrobial properties in accordance with the invention.
The hydroxyphenyl-1,3-propanediones can be used especially also in household and all-purpose cleaners for cleaning and disinfecting hard surfaces.
A cleaning preparation has, for example, the following composition:
0.01 to 5% of the compound of formula (1)
3.0% octyl alcohol 4EO
1.3% fatty alcohol C8-C10polyglucoside
3.0% isopropanol
ad 100% water.
In addition to preserving cosmetic and household products, technical products, such as paper treatment liquors, printing thickeners of starch or of cellulose derivatives, varnishes and paints, can be preserved and provided with antimicrobial properties.
The hydroxyphenyl-1,3-propanediones of formula (1) are also suitable for the antimicrobial treatment of wood and for the antimicrobial treatment of leather and the provision of leather with antimicrobial properties.
The compounds according to the invention are also suitable for the protection of cosmetic products and household products from microbial damage.
The following Examples serve to illustrate the invention but do not limit the invention to the Examples.